One of the conventional methods of measuring or detecting a concentration change in blood or the like is to take a sample of blood, separate blood cells by a blood cell separator film, a centrifugal separator, or the like, and thereafter determine the quantity of components except for the blood cells by an ordinary method.
On the other hand, when the quantity is directly determined from the interior of blood, the hemoglobin existing in the erythrocytes absorbs light in a wide wavelength band during the detection of fluorescence from a fluorescent substance (pharmaceutical agent or the like) injected into the blood, and with many pharmaceutical agents, it is thus difficult to avoid the influence of optical absorption of the hemoglobin. There are only few pharmaceutical agents the quantity of which can be determined without the influence of optical absorption of the hemoglobin.
Incidentally, Patent Document 1 (automated system and sample analysis method) discloses an optical method of utilizing fiber-optic evanescent light to detect an organic substance contained in blood or the like. This method is to remove a cladding layer of an optical fiber forming a light-detection sensor so as to generate evanescent light in a surface of the core layer, to immerse this part in a liquid sample such as the blood, to receive detected fluorescence from the liquid sample with the light-detection sensor, and to detect an organic substance in the liquid sample such as the blood through an optical addressing module.
Furthermore, Patent Document 2 (light detecting device) discloses a light detecting device utilizing an optical fiber (guide) and arranged to bring a liquid sample (blood or the like) into contact with the optical guide, to excite a light emitting substance in the evanescent field, and to measure it by a photoelectric detector.
The foregoing Patent Documents 1, 2 both enable the selective and quantitative measurement of the light emitting composition in the blood or the like by use of evanescent light, but in cited Document 1 the optical illumination system for generating the evanescent light on the film of the core by removing the cladding at the tip of the optical fiber is a popular structure and its light-receiving optical system is composed of a reflected feedback path of the optical fiber. Cited Document 2 describes that the evanescent light is generated on the surface of the optical guide and the light receiving system is the photoelectric detector provided separately on the other end side of the optical guide. Patent Documents 1, 2 both are directed in common to the technology of separately taking the liquid sample and determining the quantity.
Therefore, their configurations are unable to determine the quantity within a living organism and the erythrocytes must be separated in advance according to need in order to eliminate the influence of the hemoglobin in blood.
Important portions for implementing the determination of quantity without the influence of hemoglobin within a living organism are configurations of the illumination system and light receiving system at the tip of the optical fiber, but Patent Documents 1, 2 fail to disclose the details of special structure about the tip of optical fiber.
Now let us focus our attention to systems in which the illumination system and light receiving system are formed by sharpening the core part at the tip of optical fiber, and Patent Documents 3, 4, and 5 disclose the tip structural portions of optical fiber.
Patent Document 3 (fiber-optic sensor for measurement of absorption spectrum using total reflection, and system thereof) discloses the following technology: a part of the cladding of the optical fiber is removed as shown in FIG. 1 of Patent Document 3, a sensor part using evanescent light by total reflection is provided at the tip of the optical fiber, this sensor part is inserted into a living organism so as to bring the sensor part into direct contact with a living tissue, the evanescent light is generated at the sensor part by a light wave having propagated as repeatedly totally reflected, the evanescent light is absorbed by a chemical component of the living tissue in contact with the sensor part to change its spectrum, it is reflected by a totally reflecting film, it is again absorbed by the chemical component, and the reflected light thereof is returned through the optical fiber.
This is the technology of measuring the absorption spectrum in the living tissue, but is not to detect fluorescence from a fluorescent substance in blood. It eliminates propagation in the living tissue, thus avoids multiple scattering due to propagation to minimize the influence of scattering, and improves the accuracy of the absorption spectrum with spatial resolution.
The configuration near the cladding part at the tip of the optical fiber in cited Document 3 is one for adapting the intensity of evanescent light generated outside the cladding part to the intensity of incident light, and is able to capture a spectral change of the evanescent light varying as absorbed by the chemical component in the living tissue. It is, however, unable to capture fluorescence emitted in the region where the evanescent light is generated outside the optical fiber, by the optical fiber and to return it to the entrance side.
Patent Document 4 (optical fiber and production method thereof) describes the shape of an optical probe of a near-field optical microscope for detecting the existence of a chemical substance or the like including the blood or the like in a living tissue and, as shown in FIGS. 1, 2, 5, 7, and 8 of Patent Document 4, the core is projected in a conical shape at the tip from the cladding, and a light shield film is formed on the core and cladding surface of the projecting part except for an opening part at the tip.
The optical fiber probe of this structure is arranged to condense light by providing the light shield film on the core part of conical shape of the projecting part as well to enhance the evanescent field generated in the surface of the detection end of the core to improve the detection sensitivity.
However, since scattered light by a sample in the evanescent field is made incident into the opening part at the tip with a very small surface area as shown in FIG. 11 of Patent Document 4, it is disadvantageous in terms of collection of scattered light in a wide area and the total increase of received light power is considered to be small. Furthermore, it is not a device that directly detects the intensity of fluorescence from a fluorescent substance in a living tissue.
Furthermore, Patent Document 5 (optical fiber and production method thereof) describes an optical fiber used in a photon scanning microscope or the like for detecting the evanescent light localized in a region smaller than the wavelength of light in a surface of a substance; the optical fiber has the structure in which one end of the core is sharpened in a tapered shape, a light-shielding coating layer is formed on the surface of the sharpened core, and an opening part is formed so as to expose the tip end; light is made incident and emergent through the other end of this optical fiber; the light incident through the end of the optical fiber is condensed at the tapered portion and is projected from the opening part to the outside. This makes the evanescent light generated and scattered in proximity of the surface of the substance, and this scattered light is guided through the opening part into the core to be outputted from the other end of the optical fiber.
This configuration solved the problem of the conventional technology that the cladding diameter was much longer than the length of the detection end and the peripheral part of the cladding could collide with the surface of the sample to break the sample or the tip of the optical probe, and thereby enhances the detection efficiency of the optical probe, while preventing the peripheral part of the cladding from colliding with the surface of the sample.
This configuration is also the shape similar to that in Patent Document 4, and it is thus disadvantageous in terms of collection of scattered light and the increase of received light power is considered to be small, as described above.    Patent Document 1: Japanese Patent No. 3429282    Patent Document 2: Published Translated Version of PCT Application No. 2000-516719    Patent Document 3: Japanese Patent Application Laid-Open No. 2002-214132    Patent Document 4: Japanese Patent Application Laid-Open No. 10-2905    Patent Document 5: Japanese Patent No. 3278164